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Nat Genet. 2016 Nov;48(11):1396-1406. doi: 10.1038/ng.3695. Epub 2016 Oct 10.

Genome-wide association analysis identifies variation in vitamin D receptor and other host factors influencing the gut microbiota.

Author information

1
Evolutionary Genomics, Max Planck Institute for Evolutionary Biology, Plön, Germany.
2
Institute for Experimental Medicine, Christian Albrechts University of Kiel, Kiel, Germany.
3
Institute of Clinical Molecular Biology, Christian Albrechts University of Kiel, Kiel, Germany.
4
Norwegian PSC Research Center, Division of Surgery, Inflammatory Medicine and Transplantation, Oslo, Norway.
5
Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
6
K.G. Jebsen Inflammation Research Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
7
Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.
8
Section of Gastroenterology, Department of Transplantation Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.
9
Estonian Genome Center, University of Tartu, Tartu, Estonia.
10
Division of Gastroenterology and Hepatology, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA.
11
Department of Nutrition and Food Sciences, Nutritional Epidemiology, University of Bonn, Bonn, Germany.
12
Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
13
Department of Clinical Science, University of Bergen, Bergen, Norway.
14
Department of Heart Disease, Haukeland University Hospital, Bergen, Norway.
15
Institute of Epidemiology, Christian Albrechts University of Kiel, Kiel, Germany.
16
Institute of Human Nutrition and Food Science, University of Kiel, Kiel, Germany.
17
BioDonostia Health Research Institute, San Sebastian and Ikerbasque, Basque Foundation for Science, Bilbao, Spain.
18
Unit of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
19
Department of Internal Medicine I, University Hospital S.-H. (UKSH, Campus Kiel), Kiel, Germany.
20
Department of Clinical Medicine, University of Bergen, Bergen, Norway.

Abstract

Human gut microbiota is an important determinant for health and disease, and recent studies emphasize the numerous factors shaping its diversity. Here we performed a genome-wide association study (GWAS) of the gut microbiota using two cohorts from northern Germany totaling 1,812 individuals. Comprehensively controlling for diet and non-genetic parameters, we identify genome-wide significant associations for overall microbial variation and individual taxa at multiple genetic loci, including the VDR gene (encoding vitamin D receptor). We observe significant shifts in the microbiota of Vdr-/- mice relative to control mice and correlations between the microbiota and serum measurements of selected bile and fatty acids in humans, including known ligands and downstream metabolites of VDR. Genome-wide significant (P < 5 × 10-8) associations at multiple additional loci identify other important points of host-microbe intersection, notably several disease susceptibility genes and sterol metabolism pathway components. Non-genetic and genetic factors each account for approximately 10% of the variation in gut microbiota, whereby individual effects are relatively small.

PMID:
27723756
PMCID:
PMC5626933
DOI:
10.1038/ng.3695
[Indexed for MEDLINE]
Free PMC Article

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